1. Field of the Invention
The invention relates to gel bases or vehicles for pharmaceutical compositions, compositions incorporating such bases and methods of administering medications utilizing such bases.
2. Description of the Prior Art
Pharmaceutical agents effective in topical application, e.g. for treating dermatological conditions, generally must be incorporated into a suitable ointment, lotion or cream vehicle to promote uniform application and effective transdermal absorption.
Originally, most vehicles for topical medicaments were in the nature of greasy ointments which are not water washable and have a tendency to adhere to and stain clothing. Moreover, the greasy composition of many ointments actually inhibits the release and absorption of many topically active pharmaceutical agents.
As an alternative to ointments, water-based creams were developed which are water washable and nonstaining, and yet provide satisfactory spreadability and adherence while not inhibiting the release of active ingredients admixed therewith. These aqueous creams, however, are not suitable for use with active ingredients which are water-decomposable or water-insoluble. Furthermore, many of the aqueous creams of the prior art provide little or no occlusive coating to the treated area. In the case of certain topically active agents, such as anti-inflammatory steroids, therapeutic efficacy is substantially increased when the topical vehicle provides occlusion as well was adherence.
In order to combine the desirable unctuousness and pharmaceutical compatibility of oil-based ointments with the water miscibility and lightness of aqueous creams, anhydrous water washable bases have been developed which do not adversely affect moisture-degradable or water-insoluble ingredients, enable rapid release of the active agent and provide an occlusive coating for enhanced pharmaceutical activity. Such anhydrous creams are disclosed, for example, in U.S. Pat. Nos. 3,592,930 and 3,888,995. The specific cream vehicles described in the aforementioned patents consist primarily of propylene glycol and a saturated fatty alcohol having from 16 to 24 carbon atoms. Various plasticizers, coupling agents and penetrants are also taught as valuable additional ingredients.
While anhydrous creams disclosed in the prior art, e.g., the fatty alcohol/propylene glycol creams, are effective and have been commercially used for topical steroid preparations, they suffer from a number of drawbacks. These creams incorporate fatty alcohols having 16 or more carbon atoms, but commercially available C.sub.16 to C.sub.24 fatty alcohols contain as impurities significant amounts of unsaturated alcohols and alcohols having fewer than 16 carbon atoms. These short-chain alcohols are known irritants which may exacerbate rather than ameliorate the condition to be treated. Moreover, while propylene glycol is used in many topically active pharmaceuticals, particularly steroids (the higher the propylene glycol concentration, the less need there is for preservatives and the better the percutaneous absorption), the propylene glycol concentration in the known anhydrous creams cannot normally be increased beyond about 70% without decreasing the viscosity of the cream to the point where it resembles a lotion.
Alcohol-containing gels and gel-like vehicles for pharmaceutical agents are also known in the prior art. By way of example, U.S. Pat. No. 4,540,572 discloses a gel-like ointment containing indomethacin as well as ethyl alcohol to be applied topically, but intended to achieve systemic blood levels of the indomethacin for treatment of rheumatic diseases. Similarly, in U.S. Pat. No. 4,593,048, compositions incorporating high concentrations of lower alcohols, including such compositions in gel form, are disclosed. These prior art alcohol-containing gels, however, include extrinsic gelling agents, e.g. carboxymethyl cellulose, in addition to the alcohols and other ingredients of the pharmaceutical vehicle. Moreover, the alcohols utilized are short-chain alcohols (generally ethyl alcohol) which can be irritating, drying, and sensitizing, particularly when applied to broken or inflamed tissue areas.
Moreover, the alcohol-containing gels disclosed in the prior art would not be appropriate for transmucosal administration, for example, intranasally, buccally, or sublingually, because of the irritation and discomfort which would be caused thereby, and because of the possible detrimental effects of repeated application to the mucosa.
Gel-like formulations designed for systemic administration of pharmaceutical agents via transmucosal routes, particularly by the intranasal route, are disclosed in U.S. Pat. Nos. 4,383,993 and 4,394,390, among others. These gels, however, while innocuous and suitable for application to mucous membranes, are aqueous and therefore not usable with active ingredients that rapidly decompose or are insoluble in an aqueous vehicle and also require extrinsic gelling agents, which significantly add to the expense and time of manufacture and foster bacterial growth.